FDA finally approves 4th generation HIV Ag/Ab test in the US

On 18 June 2010, the FDA approved a new, “4th generation” HIV diagnostic assay.

The ARCHITECT HIV Ag/Ab Combo Assay is the first HIV diagnostic assay to be approved in the US that detects both antigen and antibodies for HIV.

The new test is also the first diagnostic test approved by FDA for use in children as young as 2 years of age, and pregnant women.

It is specific for the detection of the HIV-1 p24 antigen (the substance found on the virus that triggers the production of antibodies), as well as antibodies to HIV-1 groups M and O, and as antibodies to HIV-2.

Levels of p24 antigen increase early after initial infection, before HIV antibody is produced and extends diagnosis to earlier, acute phase (recent) infection with HIV, reducing the window period (that period after initial infection and before the detection of infection based on formation of detectable antibodies).

The median detection time was demonstrated to be 7 days earlier (range 0 to 20 days) compared to 3rd generation enzyme immunoassay antibody tests.


Fourth generation tests have been widely used in Europe for many years, although a handful of clinics, still use third generation despite current guidelines.

Although these tests reduce the window period between potential exposure and the opportunity to test down to 2–3 weeks, from a public health perspective, 28 days/4weeks is now possible.

Testing guidelines still refer to a six-week window by which time p-24 which peaks before 3 weeks and disappears after 2–3 months, is already fading.

Despite the widespread use of fourth generation testing, it is difficult to understand why many clinics in the UK still routinely refer to a three-month window period. This not only prolongs the anxiety for anyone who is concerned about recent exposure, but also undoubtedly misses the opportunity to diagnose some people during early infection. Many people who are concerned enough to test early, may be less likely to test three months later once their initial anxiety has abated, especially give the sometimes difficult access to walk-in, same day and out-of-hours testing services.

The British Association for Sexual Health and HIV (BASHH) guidelines on HIV testing state: [2]

“Fourth generation tests will detect the great majority of individuals who have been infected with HIV at one month (4 weeks) after specific exposure.”

“Patients attending for HIV testing who identify a specific risk occurring more that 4 weeks previously, should not be made to wait three months (12 weeks) before HIV testing. They should be offered a 4th generation laboratory HIV test and advised that a negative result at 4 weeks post exposure is very reassuring/highly likely to exclude HIV infection. An additional HIV test should be offered to all persons at three months (12 weeks) to definitively exclude HIV infection. Patients at lower risk may opt to wait until three months to avoid the need for HIV testing twice.”


  1. FDA list serve announcement. (18 June 2010).
  2. The British Association for Sexual Health and HIV (BASHH) statement on HIV window period (15 March 2010).

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